Taking a long-acting injection of cabotegravir + rilpivirine (Edurant) either every four or eight weeks is safe and well tolerated while also maintaining high viral suppression rates, according to 32-week study results presented at CROI 2016 in Boston.
Cabotegravir is an investigational integrase inhibitor (a "cousin" of dolutegravir [Tivicay, DTG]) that has shown potential as a long-acting agent. The original LATTE study found that taking oral cabotegravir + rilpivirine daily as maintenance therapy (typically a simplified regimen after viral suppression was achieved on induction therapy) was effective up to 96 weeks.
The highly anticipated follow-up study known as LATTE-2, which was presented by David A. Margolis, M.D., sought to find out if taking a long-acting injectable version of cabotegravir + rilpivirine as maintenance therapy would be safe and effective, and which dose would be best.
LATTE-2 followed 309 treatment-naive individuals living with HIV. After 20 weeks of induction-phase antiretroviral therapy using oral cabotegravir + abacavir/lamivudine (Epzicom, Kivexa), 286 individuals achieved an undetectable viral load (<50 copies/mL) and were randomized to receive maintenance therapy via an injection every four weeks (Q4W) or every eight weeks (Q8W), or to continue on the oral regimen.
Overall, the median age was 35, 92% were male, 15% were African American and the median CD4+ cell count was 489.
Virologic Suppression Outcomes
After 32 weeks, 95% of the Q8W group maintained an undetectable viral load, compared with 94% of the Q4W group and 91% of the oral group. Only one person in the Q8W group and one person in the oral group experienced virologic failure. No drug resistance developed in any of the groups.
Read: Emtricitabine/Tenofovir Alafenamide Maintains Viral Suppression With Better Bone and Kidney Safety
Injection Site Reactions
The most common drug-related adverse event was injection site reactions (ISRs) for both injection groups, commonly because of pain (67%), swelling (7%) or nodules (6%). The reactions were considered either mild or moderate, lasting a median of three days. However, the percentage of people reporting ISRs decreased as the study went on, going from 86% on day one to 33% by week 32. Only two participants in the Q8W group withdrew from the study because of ISRs.
Non-ISR Adverse Events
Low-grade, drug-related, non-ISR adverse events (including fever, fatigue and flu-like illness) were more common in the injection groups than in the oral group, though were less than 5% for each.
Grade-3/4, drug-related, non-ISR adverse events were also more common in both injection groups (3%) compared with the oral group (0%), but rare overall.
Serious adverse events were similar across all groups: 6% in the Q8W group, 5% in the Q4W group and 5% in the oral group.
Nine participants withdrew because of non-ISR adverse events: 2% in the Q8W group, 5% in the Q4W group and 2% in the oral group.
Maintenance Therapy Satisfaction
When asked how satisfied they were with their maintenance therapy versus induction therapy, 97% of the Q8W group reported being more satisfied, compared with 96% of the Q4W group and 71% of the oral group. When asked if they would continue their current form of therapy, 98% of both the Q8W and Q4W groups said they would, compared with 71% of the oral group. However, it's possible that there was already a bias based on willingness to participate in a long-acting injectable study.
Investigators administered the injections during visits to study sites. When asked if individuals would be able to self-inject the drugs, Margolis responded that it's certainly possible, perhaps in the upper thigh, but further study would be needed.
There was a one-week buffer built into either side of the injection visit, meaning there was a two-week window within which participants needed to show up for their visit. Very few participants fell outside this window, Margolis noted.
Both Q8W and Q4W doses were considered highly effective and neither was ruled out for further study. Week-48 data will provide more insight and contribute to phase-3 planning.